Integrating microfluidics, hydrogels, and 3D bioprinting for personalized vessel-on-a-chip platforms.

Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs.

Probing the Interplay of Protein Self-Assembly and Covalent Bond Formation in Photo-Crosslinked Silk Fibroin Hydrogels.

Covalent crosslinking of silk fibroin via native tyrosine residues has been extensively explored; however, while these materials are very promising for biomedical, optical, soft robotics, and sensor applications, their structure and mechanical properties are unstable over time. This instability results in spontaneous silk self-assembly and stiffening over time, a process that is poorly understood. This study investigates the interplay between self-assembly and di-tyrosine bond formation in silk hydrogels photo-crosslinked using ruthenium (Ru) and sodium persulfate (SPS) with visible light.

Design considerations for digital light processing bioprinters.

With the rapid development and popularization of additive manufacturing, different technologies, including, but not limited to, extrusion-, droplet-, and vat-photopolymerization-based fabrication techniques, have emerged that have allowed tremendous progress in three-dimensional (3D) printing in the past decades. Bioprinting, typically using living cells and/or biomaterials conformed by different printing modalities, has produced functional tissues. As a subclass of vat-photopolymerization bioprinting, digital light processing (DLP) uses digitally controlled photomasks to selectively solidify liquid photocurable bioinks to construct complex physical objects in a layer-by-layer manner.

An introduction to injectable hydrogels.

Injectable hydrogels have emerged as intelligent and versatile materials that have been proven to possess huge potential for many biomedical applications including drug delivery, tissue engineering, and regenerative medicine. Hydrogels are a class of polymers with highly hydrated 3D networks that have microenvironmental properties such as oxygen/nutrient permeability that are similar to the native extracellular matrix. In addition to possessing the typical advantages of conventional hydrogels, injectable hydrogels offer extra unique features, enabling minimally invasive injectability and durability for irregularly shaped sites, and the possibility of processing these materials , , additive manufacturing techniques.

Single-Atom-Based Nanoenzyme in Tissue Repair.

Since the discovery of ferromagnetic nanoparticles FeO that exhibit enzyme-like activity in 2007, the research on nanoenzymes has made significant progress. With the in-depth study of various nanoenzymes and the rapid development of related nanotechnology, nanoenzymes have emerged as a promising alternative to natural enzymes. Within nanozymes, there is a category of metal-based single-atom nanozymes that has been rapidly developed due to low cast, convenient preparation, long storage, less immunogenicity, and especially higher efficiency.

Programming temporal stiffness cues within extracellular matrix hydrogels for modelling cancer niches.

Extracellular matrix (ECM) stiffening is a common occurrence during the progression of many diseases, such as breast cancer. To accurately mimic the pathophysiological context of disease within 3D models, there is high demand for smart biomaterials which replicate the dynamic and temporal mechanical cues of diseased states. This study describes a preclinical disease model, using breast cancer as an example, which replicates the dynamic plasticity of the tumour microenvironment by incorporating temporal (3-week progression) biomechanical cues within a tissue-specific hydrogel microenvironment.

Bioassembly of hemoglobin-loaded photopolymerizable spheroids alleviates hypoxia-induced cell death.

The delivery of oxygen within tissue engineered constructs is essential for cell survivability; however, achieving this within larger biofabricated constructs poses a significant challenge. Efforts to overcome this limitation often involve the delivery of synthetic oxygen generating compounds. The application of some of these compounds is problematic for the biofabrication of living tissues due to inherent issues such as cytotoxicity, hyperoxia and limited structural stability due to oxygen inhibition of radical-based crosslinking processes.

Harnessing Macromolecular Chemistry to Design Hydrogel Micro- and Macro-Environments.

Cell encapsulation within three-dimensional hydrogels is a promising approach to mimic tissues. However, true biomimicry of the intricate microenvironment, biophysical and biochemical gradients, and the macroscale hierarchical spatial organizations of native tissues is an unmet challenge within tissue engineering. This review provides an overview of the macromolecular chemistries that have been applied toward the design of cell-friendly hydrogels, as well as their application toward controlling biophysical and biochemical bulk and gradient properties of the microenvironment.

Comprehensive Matrisome Profiling of Human Adipose Tissue for Soft Tissue Reconstruction.

For effective translation of research from tissue engineering and regenerative medicine domains, the cell-instructive extracellular matrix (ECM) of specific tissues must be accurately realized. As adipose tissue is gaining traction as a biomaterial for soft tissue reconstruction, with highly variable clinical outcomes obtained, a quantitative investigation of the adipose tissue matrisome is overdue. In this study, the human adipose tissue matrisome is profiled using quantitative sequential windowed acquisition of all theoretical fragment ion spectra - mass spectrometry (SWATH-MS) proteomics across a cohort of 13 fat-grafting patients, to provide characterization of ECM proteins within the tissue, and to understand human population variation.

Pristine gelatin incorporation as a strategy to enhance the biofunctionality of poly(vinyl alcohol)-based hydrogels for tissue engineering applications.

Synthetic polymers, such as poly(vinyl alcohol) (PVA), are popular biomaterials for the fabrication of hydrogels for tissue engineering and regenerative medicine (TERM) applications, as they provide excellent control over the physico-chemical properties of the hydrogel. However, their bioinert nature is known to limit cell-biomaterial interactions by hindering cell infiltration, blood vessel recruitment and potentially limiting their integration with the host tissue. Efforts in the field have therefore focused on increasing the biofunctionality of synthetic hydrogels, without limiting the advantages associated with their tailorability and controlled release capacity.

Flexible Allyl-Modified Gelatin Photoclick Resin Tailored for Volumetric Bioprinting of Matrices for Soft Tissue Engineering.

Volumetric bioprinting (VBP) is a light-based 3D printing platform, which recently prompted a paradigm shift for additive manufacturing (AM) techniques considering its capability to enable the fabrication of complex cell-laden geometries in tens of seconds with high spatiotemporal control and pattern accuracy. A flexible allyl-modified gelatin (gelAGE)-based photoclick resin is developed in this study to fabricate matrices with exceptionally soft polymer networks (0.2-1.

3D Volumetric Mechanosensation of MCF7 Breast Cancer Spheroids in a Linear Stiffness Gradient GelAGE.

The tumor microenvironment presents spatiotemporal shifts in biomechanical properties with cancer progression. Hydrogel biomaterials like GelAGE offer the stiffness tuneability to recapitulate dynamic changes in tumor tissues by altering photo-energy exposures. Here, a tuneable hydrogel with spatiotemporal control of stiffness and mesh-network is developed.

Clinical Applicability of Visible Light-Mediated Cross-linking for Structural Soft Tissue Reconstruction.

Visible light-mediated cross-linking has utility for enhancing the structural capacity and shape fidelity of laboratory-based polymers. With increased light penetration and cross-linking speed, there is opportunity to extend future applications into clinical spheres. This study evaluated the utility of a ruthenium/sodium persulfate photocross-linking system for increasing structural control in heterogeneous living tissues as an example, focusing on unmodified patient-derived lipoaspirate for soft tissue reconstruction.

Combined Growth Factor Hydrogel Enhances Rotator Cuff Enthesis Healing in Rat But Not Sheep Model.

We hypothesized that a combined growth factor hydrogel would improve chronic rotator cuff tear healing in a rat and sheep model. Insulin-like growth factor 1, transforming growth factor β1, and parathyroid hormone were combined into a tyraminated poly-vinyl-alcohol (PVA-Tyr) hydrogel and applied directly at the enthesis. In total, 30 Sprague-Dawley rats and 16 Romney ewes underwent unilateral rotator cuff tenotomy and then delayed repairs were performed after 3-4 weeks.

Engineering Cell Microenvironment Using Nanopattern-Derived Multicellular Spheroids and Photo-Crosslinked Gelatin/Hyaluronan Hydrogels.

Cell cultures of dispersed cells within hydrogels depict the interaction of the cell-extracellular matrix (ECM) in 3D, while the coculture of different cells within spheroids combines both the effects of cell-cell and cell-ECM interactions. In this study, the cell co-spheroids of human bone mesenchymal stem cells/human umbilical vein endothelial cells (HBMSC/HUVECs) are prepared with the assistance of a nanopattern, named colloidal self-assembled patterns (cSAPs), which is superior to low-adhesion surfaces. A phenol-modified gelatin/hyaluronan (Gel-Ph/HA-Ph) hydrogel is used to encapsulate the multicellular spheroids and the constructs are photo-crosslinked using blue light.

Harnessing light in biofabrication.

The integration of light-driven technologies into biofabrication has revolutionized the field of tissue engineering and regenerative medicine, with numerous breakthroughs in the last few years. Light-based bioprinting approaches (lithography, multiphoton and volumetric bioprinting) have shown the potential to fabricate large scale tissue engineering constructs of high resolution, with great flexibility and control over the cellular organization. Given the unprecedented degree of freedom in fabricating convoluted structures, key challenges in regenerative medicine, such as introducing complex channels and pre-vascular networks in 3D constructs have also been addressed.

High resolution lithography 3D bioprinting.

Lithography bioprinting can fabricate constructs with high resolution for potential use in tissue engineering applications. Seminal work by Grigoryan and colleagues developed bioresins with precise control over the x, y, and z-planes during lithography bioprinting and applied this technique to fabricating physiologically biomimetic alveolar lung models.

Surface Biofunctionalization of Silk Biomaterials Using Dityrosine Cross-Linking.

Biofunctionalization of silk biomaterial surfaces with extracellular matrix (ECM) molecules, cell binding peptides, or growth factors is important in a range of applications, including tissue engineering and development of implantable medical devices. Passive adsorption is the most common way to immobilize molecules of interest on preformed silk biomaterials but can lead to random molecular orientations and displacement from the surface, limiting their applications. Herein, we developed techniques for covalent immobilization of biomolecules using enzyme- or photoinitiated formation of dityrosine bonds between the molecule of interest and silk.

GelMA Hydrogel Reinforced with 3D Printed PEGT/PBT Scaffolds for Supporting Epigenetically-Activated Human Bone Marrow Stromal Cells for Bone Repair.

Epigenetic approaches using the histone deacetylase 2 and 3 inhibitor-MI192 have been reported to accelerate stem cells to form mineralised tissues. Gelatine methacryloyl (GelMA) hydrogels provide a favourable microenvironment to facilitate cell delivery and support tissue formation. However, their application for bone repair is limited due to their low mechanical strength.

The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy.

Dyslipidemia, characterized by a high level of lipids (cholesterol, triglycerides, or both), can increase the risk of developing and progressing atherosclerosis. As atherosclerosis progresses, the number and severity of aterial plagues increases with greater risk of myocardial infarction, a major contributor to cardiovascular mortality. Atherosclerosis progresses in four phases, namely endothelial dysfunction, fatty streak formation, lesion progression and plaque rupture, and eventually thrombosis and arterial obstruction.